Evidence map›Paper›PMID 29563501›Full record

ArticleNature communications2018

Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes.

David S Hewings, Johanna Heideker, Taylur P Ma, Andrew P AhYoung, Farid El Oualid, Alessia Amore, Gregory T Costakes, Daniel Kirchhofer, Bradley Brasher, Thomas Pillow and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 86 citations in OpenAlex.

  1. Synthetic Strategies for Activity-Based Probes to Decode Ubiquitin-Like Modifiers.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  10. Article
  11. Cocrystallization of ubiquitin-deubiquitinase complexes through disulfide linkage.Acta crystallographica. Section D, Structural biology · 2023
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 2 countries.

David S HewingsDiscovery Oncology, Genentech, South San Francisco, California, 94080, USA.ORCID http://orcid.org/0000-0001-9451-8959
Johanna HeidekerDiscovery Oncology, Genentech, South San Francisco, California, 94080, USA.
Taylur P MaMicrochemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, 94080, USA.
Andrew P AhYoungEarly Discovery Biochemistry, Genentech, South San Francisco, California, 94080, USA.
Farid El OualidUbiQ Bio BV, Science Park 408, 1098 XH, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-4447-9960
Alessia AmoreUbiQ Bio BV, Science Park 408, 1098 XH, Amsterdam, The Netherlands.
Gregory T CostakesBoston Biochem Inc., 840 Memorial Drive, Cambridge, Massachussetts, 02139, USA.
Daniel KirchhoferEarly Discovery Biochemistry, Genentech, South San Francisco, California, 94080, USA.ORCID http://orcid.org/0000-0002-0975-4402
Bradley BrasherBoston Biochem Inc., 840 Memorial Drive, Cambridge, Massachussetts, 02139, USA.
Thomas PillowDiscovery Chemistry, Genentech, South San Francisco, California, 94080, USA.ORCID http://orcid.org/0000-0001-7300-1002
Nataliya PopovychEarly Discovery Biochemistry, Genentech, South San Francisco, California, 94080, USA.
Till MaurerStructural Biology, Genentech, South San Francisco, California, 94080, USA.
Carsten SchwerdtfegerBoston Biochem Inc., 840 Memorial Drive, Cambridge, Massachussetts, 02139, USA.
William F ForrestBioinformatics, Genentech, South San Francisco, California, 94080, USA.
Kebing YuMicrochemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, 94080, USA.
John FlygareDiscovery Chemistry, Genentech, South San Francisco, California, 94080, USA.
Matthew BogyoDepartment of Pathology, Stanford University School of Medicine, Stanford, California, 94305, USA.
Ingrid E WertzDiscovery Oncology, Genentech, South San Francisco, California, 94080, USA. wertz.ingrid@gene.com.
Stanford University · USGene Therapy Laboratory · FRMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

Equipment supplement for Chemical methods to study protein palmitoylation pathwaysR01GM111703 · NIGMS · STANFORD UNIVERSITY · PI BOGYO, MATTHEW · 2014 to 2017
$1.6M
NIGMS NIH HHS R01 GM111703
6 · The paper itself

Abstract

Activity-based probes (ABPs) are widely used to monitor the activity of enzyme families in biological systems. Inferring enzyme activity from probe reactivity requires that the probe reacts with the enzyme at its active site; however, probe-labeling sites are rarely verified. Here we present an enhanced chemoproteomic approach to evaluate the activity and probe reactivity of deubiquitinase enzymes, using bioorthogonally tagged ABPs and a sequential on-bead digestion protocol to enhance the identification of probe-labeling sites. We confirm probe labeling of deubiquitinase catalytic Cys residues and reveal unexpected labeling of deubiquitinases on non-catalytic Cys residues and of non-deubiquitinase proteins. In doing so, we identify ZUFSP (ZUP1) as a previously unannotated deubiquitinase with high selectivity toward cleaving K63-linked chains. ZUFSP interacts with and modulates ubiquitination of the replication protein A (RPA) complex. Our reactive-site-centric chemoproteomics method is broadly applicable for identifying the reaction sites of covalent molecules, which may expand our understanding of enzymatic mechanisms.

Indexed as

Protein Processing, Post-TranslationalBiocatalysisCatalytic DomainCysteineDeubiquitinating EnzymesHEK293 CellsHeLa CellsHumansLysineMolecular ProbesProteomicsReplication Protein AStaining and LabelingSumoylationUbiquitinationCysteineDeubiquitinating EnzymesLysineMolecular ProbesReplication Protein ARPA1 protein, humanZUP1 protein, human

Identifiers

PMID29563501
PMCPMC5862848
OpenAlexW2789777795

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.